Persistent but mild hyperketonemia is common in newborn mammals, including man. Although ketone bodies are known to be a ready source of energy for developing extrahepatic tissues, their contribution to biosynthetic processes has not been fully determined. Recent evidence from our laboratory, as well as others, indicates that ketones can be incorporated into fatty acids and complex lipids in the brain of suckling rats and human fetuses. Since brain maturation includes a myelination process that relies on fatty acids and on the synthesis of sphingolopids and phospholipids, ketone bodies could contribute significantly to brain development. We propose to assess the role of ketone bodies as precursors fro the synthesis of cerebral lipids in developing rats. The fatty acid composition of various lipid classes synthesized from 14C-labeled ketones will be determined and compared with that found in different regions of the brain from developing rats. The contribution of cytoplasmic acetoacetyl CoA synthetase versus ATP-citrate lyase pathways in generating acetyl CoA from ketones for lipogenesis will be evaluated. We also intend to determine (1) whether acetyl CoA and malonyl CoA derived from ketones are utilized preferentially or equally for chain elongation and de novo synthesis of fatty acids, and (2) the effects of undernutrition and maternal diets on the synthesis of lipid from ketones in the brain of fetuses and suckling rats.